Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-κB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation
- PMID: 20170972
- DOI: 10.1016/j.radonc.2010.01.013
Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-κB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation
Abstract
Background and purpose: This study aimed to characterize a link between X-linked inhibitor of apoptosis protein (XIAP) expression, apoptosis induction, Nuclear Factor kappa B (NF-κB) activity and the anti-inflammatory properties of low-dose ionising-radiation (LD-RT).
Material and methods: EA.hy.926 endothelial cells (ECs) were irradiated with doses ranging from 0.3 to 3Gy, and subsequently stimulated by TNF-α, and XIAP expression was either detected by immunoblotting or TaqMan-PCR. Apoptosis was quantified by AnnexinV staining or by caspase 3/7 activity assays. NF-κB transcriptional activity was analysed by a luciferase reporter assay, secretion of Transforming Growth Factor beta 1 (TGF-β(1)) and adhesion of peripheral blood mononuclear cells (PBMC) to EC were quantified using ELISA and adhesion assays.
Results: LD-RT of the activated EA.Hy.926 EC induces XIAP expression in a discontinuous manner with a relative maximum at 0.5Gy and 3Gy which parallels a discontinuity in apoptosis induction and caspase 3/7 activity. siRNA-mediated attenuation of XIAP resulted in an increased rate of apoptosis, a hampered NF-κB transcriptional activity and a diminished secretion of TGF-β(1). As compared to control-siRNA treated cells, adhesion of PBMC to EC was increased in XIAP depleted EA.Hy.926 EC.
Conclusion: The modulation of apoptosis, NF-κB activity and TGF-β(1) by XIAP in irradiated and subsequent stimulated EC contributes to an impaired PBMC/EC adhesion and to the anti-inflammatory properties of LD-RT.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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